A novel tumor-associated neutrophil gene signature for predicting prognosis, tumor immune microenvironment, and therapeutic response in breast cancer.

Tumor-associated neutrophils (TANs) can promote tumor progression. This study aimed to investigate the molecular signature that predict the prognosis and immune response of breast cancer (BRCA) based on TAN-related gene (TANRG) expression data. The RNA-seq data of BRCA were gathered from The Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO) datasets. Univariate Cox regression analysis and the least absolute shrinkage and selection operator for selecting prognostic genes. A neo-TAN-related risk signature was constructed by multivariate Cox regression analysis. Time-dependent receiver operating characteristic (ROC) curve analyses and Kaplan-Meier analyses were performed to validate the signature in GEO cohorts and the triple-negative breast cancer (TNBC) subtype. We constructed an independent prognostic factor model with 11 TANRGs. The areas under the ROC curve (AUCs) of the TCGA training cohorts for 3-, 5-, and 7-year overall survival were 0.72, 0.73, and 0.73, respectively. The AUCs of the GEO test cohorts for 3-, 5-, and 7-year overall survival were 0.83, 0.89, and 0.94 (GSE25066) and 0.67, 0.69, and 0.73 (GSE58812), respectively. The proportion of immune subtypes differed among the different risk groups. The IC50 values differed significantly between risk groups and can be used as a guide for systemic therapy. The prognostic model developed by TANRGs has excellent predictive performance in BRCA patients. In addition, this feature is closely related to the prediction of survival, immune activity and treatment response in BRCA patients.

[A clinical study of paclitaxel combined with FOLFOX4 regimen as neoadjuvant chemotherapy for advanced gastric cancer].

OBJECTIVE: To evaluate the clinical efficacy and the toxicity of neoadjuvant chemotherapy with paclitaxel and FOLFOX4 (5-fluorouracil/leucovorin combined and oxaliplatin) regimen for advanced gastric cancer. METHODS: Seventy-eight patients with cTNM stage III or IV (M0) gastric cancer were enrolled and 39 were randomized into the treatment arm (n=39, paclitaxel combined with FOLFOX4 regimen neoadjuvant chemotherapy every two weeks in each cycle) and control group (n=39). Clinical response was evaluated with RECIST criteria after 3 cycles. Patients in experimental group received surgery after 2-4 weeks and postoperative chemotherapy of 3 cycles of the original regimen. When disease progressed, postoperative chemotherapy regimen was changed into ECF regimen. The control group of 39 patients received surgery within 2 weeks and postoperative chemotherapy of 6 cycles of paclitaxel combined with FOLFOX4 regimen. RESULTS: The clinical response rate was 66.7% in the treatment arm. The R0 resection rate (59.0%) was significantly higher than that in the control group (P=0.025) and the number of lymph node metastasis in the treatment arm(3.23±2.80) was significantly lower than that in the control group (5.79±2.69, P=0.001). There were no significant differences in postoperative complication rate (5.1% vs. 2.6%) and the number of lymph node dissection (19.69±2.95 vs. 20.59±3.22) between the two groups (P>0.05). The median survival time and 2-year survival rate in the treatment arm [(27.10±2.32) months and 59.0%] was significantly higher than that in the control group[(18.20±1.30) months and 28.2%] (P=0.001, P=0.006). Cox regression multivariable analysis showed that tumor differentiation, R0 resection, lymph node metastasis were independent prognostic factors. Adverse reaction of chemotherapy, mainly hematological adverse reactions, and peripheral nerve toxicity, were tolerable. No significant differences were noted between the two groups in adverse reactions (P>0.05). CONCLUSIONS: The efficacy of paclitaxel combined with FOLFOX4 as neoadjuvant chemotherapy is high. Patients tolerance and compliance are satisfactory. It can improve in patients with advanced gastric cancer the R0 resection rate, reduce lymph node metastasis and improve survival.